Prenatal Exposure to Alcohol Induces Functional and Structural Plasticity in Dopamine D1 Receptor-Expressing Neurons of the Dorsomedial Striatum. Academic Article uri icon


  • BACKGROUND: Prenatal alcohol exposure (PAE) is a leading cause of hyperactivity in children. Excitation of dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) of the dorsomedial striatum (DMS), a brain region that controls voluntary behavior, is known to induce hyperactivity in mice. We therefore hypothesized that PAE-linked hyperactivity was due to persistently altered glutamatergic activity in DMS D1-MSNs. METHODS: Female Ai14 tdTomato reporter mice were given access to alcohol in an intermittent access, 2-bottle choice paradigm before pregnancy, and following mating with male D1-Cre mice, through the pregnancy period, and until postnatal day (P) 10. Locomotor activity was tested in juvenile (P21) and adult (P133) offspring, and alcohol-conditioned place preference (CPP) was measured in adult offspring. Glutamatergic activity in DMS D1-MSNs of adult PAE and control mice was measured by slice electrophysiology, followed by measurements of dendritic morphology. RESULTS: Our voluntary maternal alcohol consumption model resulted in increased locomotor activity in juvenile PAE mice, and this hyperactivity was maintained into adulthood. Furthermore, PAE resulted in a higher alcohol-induced CPP in adult offspring. Glutamatergic activity onto DMS D1-MSNs was also enhanced by PAE. Finally, PAE increased dendritic complexity in DMS D1-MSNs in adult offspring. CONCLUSIONS: Our model of PAE does result in persistent hyperactivity in offspring. In adult PAE offspring, hyperactivity is accompanied by potentiated glutamatergic strength and afferent connectivity in DMS D1-MSNs, an outcome that is also consistent with the observed increase in alcohol preference in PAE offspring. Consequently, a PAE-sensitive circuit, centered within the D1-MSN, may be linked to behavioral outcomes of PAE.

published proceedings

  • Alcohol Clin Exp Res

altmetric score

  • 0.25

author list (cited authors)

  • Cheng, Y., Wang, X., Wei, X., Xie, X., Melo, S., Miranda, R. C., & Wang, J.

citation count

  • 16

complete list of authors

  • Cheng, Yifeng||Wang, Xuehua||Wei, Xiaoyan||Xie, Xueyi||Melo, Sebastian||Miranda, Rajesh C||Wang, Jun

publication date

  • June 2018